P1219: ZANUBRUTINIB, LENALIDOMIDE PLUS R-CHOP (ZR2-CHOP) AS THE FIRST-LINE TREATMENT FOR NON-GCB DIFFUSED LARGE B-CELL LYMPHOMA (DLBCL)
Authors: H. Zhu, Y. Sha, Y. Miao, S. Qin, W. Wu, J. Qiu, H. Mi, Y. Yang, C. Peng, C. Ding, Z. Wang, L. Fan, W. Xu, J. Li
Journal: HemaSphere (2022)

Background: R-CHOP is the standard first-line therapy of DLBCL. Although over half of patients have been cured under R-CHOP, the remaining patients shared poor prognosis with median OS less than 1 year when progression after front-line treatment. Aims: To evaluate the safety and efficacy of zanubrutinib, lenalidomide plus R-CHOP (ZR2-CHOP) as the first-line treatment for non-GCB DLBCL patients, we updated the results in our cohort. Methods: We enrolled patients aged 18 to 75 with high-risk non-GCB DLBCL (including double expression and other molecular characteristics). Oral zanubrutinib was given continuously (160mg twice daily) from Day 0, lenalidomide 25mg daily Day 1-7. Patients were administered intravenously rituximab (375mg/m2 Day 0), cyclophosphamide (750mg/m2 Day 1), doxorubicin (50mg/m2 Day 1), vincristine (1.4mg/m2 Day 1), and oral prednisone (100mg Day 1-5). All patients were recommended to receive 6 cycles of ZR2-CHOP (R-CHOP or R2-CHOP were allowed in cycle 1 due to poor physical condition or inaccessible molecular characteristics at treatment) and patients older than 70 years old were administered ZR2-miniCHOP. Prophylaxis was mandatory with G-CSF in all patients and entecavir in patients with seropositive occult HBV (HBsAg negative but HBcAb positive). CT or PET-CT scans were applied to mid-term efficacy and PET-CT scan was conducted after 6 cycles. ctDNA was dynamically detected baseline, after 3 and 6 cycles to evaluate tumor mutational burden. The primary endpoint was complete response ratio (CRR) at mid-term and after 6 cycles. The secondary endpoint was overall response rate (ORR), ctDNA dynamics and adverse events (AE). AEs were graded based on CTCAE (version 5.0). Results: 18 treatment-naïve non-GCB DLBCL patients were enrolled in this cohort between July 2020 and December 2021. The median age was 57.5 and all patients had ECOG-PS ≤2. 14 patients were diagnosed as double-expression (Table 1). At data cutoff (1st February, 2022), the median follow-up was 11 (2-19) months with 16 patients have completed 6 cycles. The ORR was 100.0%, with 15 patients achieved CR and 1 patients achieved PR (R-CHOP in cycle 1 due to poor physical condition) after 3 cycles and all of them achieved CR after 6 cycles (Figure 1). 4 patients have received autologous stem cell transplantation for consolidation after 6 cycles. ctDNA was dynamically detected in 14 patients (2 MCD subtype patients, 1 N1 patient, 1 BN2 patient, 1 A53 patient and 5 patients sharing TP53 mutation or deletion, Figure 2). 13 patients showed undetectable ctDNA after 3 cycles while 1 patient with TP53 p.R248W mutation remained detectable after 3 cycles and vanished after 6 cycles (Figure 3). During end of treatment follow-up, all patient remained CR. The most common hematological toxicity events were lymphocytes count decreased, neutrophil count decreased, thrombocytopenia and anemia, with 3-4 level occurrence rate 68.8%, 43.8%, 43.8% and 25.0%. The most common non-hematological toxicity events were nausea, fatigue and anorexia. Two patients discontinued ZR2-CHOP regimen during treatment, one with R-CHOP in last two cycles due to drug rash and HBV reactivation. Another one with Rituximab in last cycle due to lumbar vertebra fracture. Image:Summary/Conclusion: ZR2-CHOP for high-risk non-GCB DLBCL patients with fair physical condition could achieve high CRR and early-stage undetectable ctDNA. The overall tolerability was under control. The multi-center, prospective, phase II clinical trial to evaluate safety and efficacy of ZR2-CHOP as first-line treatment of intermediate- to high-risk non-GCB DLBCL is now in progress (NCT05200312).